Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon-Free Therapy

Abstract

Background and aims: Sustained virologic response (SVR) to interferon (IFN)-free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN-free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH.

Approach and results: The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow-up [FU]) IFN-free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08-1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC], < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86-0.92) in most patients, especially if assessed in a sequential manner.

Conclusions: Reassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An "immediate" HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance.

Figure 1

Cumulative incidence of hepatic decompensation after treatment according to (A) BL and (B) FU HVPG strata.

Figure 2

Cumulative incidence of hepatic decompensation after treatment according to HVPG decrease ≥ 10% from BL to FU. (A) All patients with CSPH at BL, (B) all patients with CSPH at BL, only considering events that occurred after the FU HVPG measurement, and subgroups of patients with (C) compensated CSPH and (D) decompensated CSPH at BL.

Figure 3

Performance of noninvasive markers for diagnosing CSPH at FU. Bold lines indicate parameters statistically significantly associated with the condition. (A) All patients (AUROC: *0.92; **0.816, i.e., 1 minus 0.184, due to indirect association; ***0.807; ****0.877). (B) Subgroup of patients with CSPH at BL (AUROC: *0.86; **0.836, i.e., 1 minus 0.164, due to indirect association; ***0.822; ****0.876).

Figure 4

Evolution of HVPG in 13 patients who underwent an additional (“last”) HVPG measurement after the first FU measurement and correlation with hepatic decompensation after treatment.